ヒト癌におけるP16-COK-Rb細胞回転異常に関する病理学的研究

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Expression of cell cycle regulatory proteins in both the RB and p53 pathways were investigated in lung, esophageal and oral cancers using immunohisto-chemical techniques. In squamous cell carcinoma (SCC) of lung, abnormality of p16 expression was prominent at the frequency of 78% in the RB pathway. On the other hand, strong and diffuse p53 immunoreactivity was seen in 60% of SCCs, which seemed to have point mutation of the p53 gene. In comparing clinicopathological status with the immunohistochemical results, strong p53 expression was frequently observed in higher stages of SCC, with the developing tumor located in the central field of the lung. Similarly, the frequency of p14ARF expression was high in centrally developed SCC.In stage I adenocarcinoma of the lung, abnormality of the RB pathway was not frequent. However, abnormal expression of p14ARF and MDM2 was characteristic features in the p53 pathway. Overexpression of MDM2 protein was characteristic feature in stage I adenocarcinomas, especially in well differentiated ones. These findings elucidate that cell cycle abnormality is mostly depend on p53 pathway other than RB pathway in stage I adenocarcinomas of lung.The abnormality of both RB and p53 pathways was also observed in esophageal and oral squamous cell carcinomas. Therefore, abnormality in RB and p53 pathways was essential for development of human cancers.